The long-range objective of this research program is to determine the nature and mechanisms by which the central nervous system controls the volume and composition of the extracellular fluid. Present emphasis is on the control of urinary water and sodium excretion, but thirst and salt appetite will be considered when relevant. Of equal interest is the central integration of the salt and water controlling systems, respectively, their response to various stresses, their strategy of priorities, and their interdependence. Finally, an understanding is sought of the pathogenesis of the hypo and hypernatremic states encountered clinically from CNS disease, as well as a rational approach to their correction. Our experimental approaches include acute and chronic lesions of putative central receptor mechanisms, and monitoring their effect on normal fluid and electrolyte balance, the response to osmotic and saline stresses, body fluid composition, and renal excretory patterns. Studies will also include surgical isolation of the forebrain (with its central receptors and integrating mechanisms) from the hindbrain and/or hypophysis to detect the existence of possible humoral effector mechanism of forebrain origin on sodium excretion. Additional studies include electrical recording from putative receptor loci in the ventricular wall as well as special studies of the electrical activity of the neurohypophysis, correlating unit firing rates with hormone levels, to help elucidate the control mechanism of the supraopticohypophysial units. Future studies include measurement of adenohypophysial hormones (MSF, prolactin, etc.) and assessment of their role in electrolyte metabolism, and special anatomical studies of the fiber systems ending in the neurohypophysis.